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Department of biochemistry and Molecular biology

Lee Chao, PhD

ProfessorLee Chao, PhD
Biochemistry and Molecular Biology

1971-1974      Postdoctoral Research, University of Connecticut

Education
1970                 Ph.D., Iowa State University

Contact Info
Email:
chaol@musc.edu
Office: 843-792-5786
Lab: 843-792-6748
Fax: 843-792-1627
BSB-535C

Research Interests

My laboratory's current research effort focuses on four areas. The first is to analyze the structure, organization and regulation of the genes involved in the kallikrein-kinin system. The primary function of kallikrein is to cleave low molecular weight kininogen to produce the vasoactive kinin peptide. We are analyzing the promoter of kallikrein genes by gel retardation assays and foot-printing analysis and probing the function of the kallikrein-kinin system by transgenic analysis and by homologous recombination. A number of transgenic mouse lines expressing the human tissue kallikrein gene have been generated for functional studies. Second, we are using genetically hypertensive animal models to explore the role of the kallikrein-kinin system in hypertension and to clone the defective kallikrein gene from the hypertensive animal to study the genetic defects at the molecular level. Hypertensive human populations and selected pedigrees are used to evaluate kallikrein-kinin genotypes as potential risk factors in essential hypertension and to use genotyping as a tool to identify individuals who may be predisposed to the risk factors for intervention and treatment. Third, we are developing gene delivery techniques as a tool for studying gene expression in vivo. We have successfully delivered various constructs into rat muscle, kidney, heart, lung, brain and vasculature for direct biochemical, molecular biological and physiological studies. Further development of the delivery technology could make it widely applicable for studying gene function, regulation and interaction at molecular, cellular and organismal levels. Four, we are exploring somatic gene therapy for cardiovascular and hypertensive diseases. A major objective is to improve the vector system for long-term expression in vivo. In addition, we are exploring the potential of using gene delivery to prevent tissue damage such as kidney damage caused by high salt diet and damage to the heart caused by ischemia and reperfusion.

Recent Publications

1. Zhu H, Chao J, Kotak I, Guo D, Rarikh S, Bhagatwala J, Patel SY, Houk C, Chao L, Dong Y. (2013) Plasma kallistatin is associated with adiposity and cardiometabolic risk in apparently healthy African American adolescents. Metabolism, in press.

2. Yao YY, Sheng CF, Li Y, Cong F, Ma G., Liu N, Chao J, Chao L. (2013) Tissue kallikrein-modified human endothelial progenitor cell implantation improves cardiac function via enhanced activation of Akt and increased angiogenesis. Laboratory Investigation, in press.

3. Yao YY, Li Y, Sheng Z, Yan F, Ma G, Liu N, Chao J, Chao L. (2012) Tissue kallikrein promotes cardiac neovascularization by enhancing endothelial progenitor cell migration and functional capacity. Human Gene Therapy, in press. PMID: 22435954

4. Liu YY, Bledsoe G, Hagiwara M, Shen B, Chao L, Chao J. (2012) Depletion of endogenous kallistatin exacerbates renal and cardiovascular oxidative stress, inflammation and organ remodeling. Am. J physiology, 303(8):F1230-1238.

5. Liu YY, Hagiwara M, Bledsoe G, Yang Z, Shen B, Chao L, Chao J. (2010) Blockade of endogenous tissue kallikrein aggravates renal injury by enhancing oxidative stress and inhibiting matrix degradation. Am J Physiol Renal Physiol. 298:F1033-40. PMID: 20089675

6. Shen B, Chao L, Chao J. (2010) Pivotal role of JNK-dependent FOXO1 activation in down-regulation of kallistatin expression by oxidative stress. Am J Physiol Heart Circ Physiol. 298:H1048-54. PMID: 20081110

7. Yin H, Gao L, Shen B, Chao L, Chao J. (2010)  Kallistatin Inhibits Vascular Inflammation by Antagonizing Tumor Necrosis Factor-{alpha}-Induced Nuclear Factor {kappa}B Activation. Hypertension 56:260-267. PMID: 20566960.

8. Gao L, Smith RS, Chen LM, Chai KX, Chao L, Chao J. (2010)
Tissue kallikrein promotes prostate cancer cell migration and invasion via protease-activated receptor-1-dependent signaling pathway. Biol Chem. 391-803-812. PMID: 20482314.

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